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Parkinson Disease: HELP
Articles by Jan Petter Larsen
Based on 68 articles published since 2010
(Why 68 articles?)
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Between 2010 and 2020, J. P. Larsen wrote the following 68 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Parkinson's disease and age: The obvious but largely unexplored link. 2015

Abdullah, Rashed / Basak, Indranil / Patil, Ketan S / Alves, Guido / Larsen, Jan Petter / Møller, Simon Geir. ·Department of Biological Sciences, St John's University, New York, NY, USA. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Department of Biological Sciences, St John's University, New York, NY, USA; The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. Electronic address: mollers@stjohns.edu. ·Exp Gerontol · Pubmed #25261764.

ABSTRACT: Parkinson's disease is a chronic, progressive neurodegenerative disorder with increased prevalence in the aging population. It is estimated that approximately 1.5 million individuals in the US alone suffer from Parkinson's disease and with the extension of life expectancy this number is expected to rise dramatically within the next twenty-five years. The majority of Parkinson's disease cases are sporadic. But mutations in genes such as α-synuclein, Parkin, PINK1, DJ-1 and LRRK2, have been conclusively associated with both early- and late-onset of the disease. Although the genetics of Parkinson's disease is starting to become unraveled, the interplay between genetic and environmental factors is largely unknown as are the underlying mechanisms that trigger the disease as the brain ages. The risk of Parkinson's disease increases dramatically in individuals over the age of 60 and it is estimated that more than 1% of all seniors have some form of the condition. In this review, we will highlight some of the central proteins associated with Parkinson's disease and how they may be linked to processes and factors associated with age.

2 Review Are dysautonomic and sensory symptoms present in early Parkinson's disease? 2010

Tysnes, O-B / Müller, B / Larsen, J P. ·Department of Neurology, Haukeland University Hospital, Bergen, Norway. obty@haukeland.no ·Acta Neurol Scand Suppl · Pubmed #20586740.

ABSTRACT: Parkinson's disease (PD) occurs with an annual incidence of 13/100.000, is slightly more frequent in men and is characterized by the motor symptoms tremor, rigidity, bradykinesia and postural instability. In addition, non-motor symptoms have been increasingly connected to the disease although already described in James Parkinson's 'Essay on the shaking palsy' from 1817. The motor symptoms in PD are related to the degeneration of dopaminergic cells in the substantia nigra (SN). These symptoms respond well to dopaminergic substitution. It is much more unclear whether non-motor symptoms like dysautonomia, insomnia, day-time sleepiness, fatigue, pain and neuropsychiatric symptoms respond to levodopa. Autonomic symptoms include dizziness because of orthostatic hypotension, constipation, nausea, voiding symptoms and increased sweating. Such symptoms as well as sensory symptoms like hyposmia and pain are very frequently reported in PD and seem to occur early in the disease process. Braak proposed a sequential model of neuropathology in PD starting with affection of the olfactory bulb and the autonomic innervation of the heart and gut. Affection of SN is seen from Braak stage 3, and limbic and cortical structures are affected in the later stages of the disease. Currently, the evidence for sensory and autonomic involvement in PD is reviewed with special focus on the early phase of the disease.

3 Clinical Trial Combined Diffusion Tensor Imaging and Arterial Spin Labeling as Markers of Early Parkinson's disease. 2016

Wei, Xiaobo / Yan, Ronghua / Chen, Zhaoyu / Weng, Ruihui / Liu, Xu / Gao, Huimin / Xu, Xiaofeng / Kang, Zhuang / Liu, Zhexing / Guo, Yan / Liu, Zhenhua / Larsen, Jan Petter / Wang, Jin / Tang, Beisha / Hallett, Mark / Wang, Qing. ·Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, China. · Department of Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600, Guangzhou, Guangdong 510630, China. · School of biomedical Engineering, Southern Medical University, Guangzhou, Guangdong 510515, China. · Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, #74 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China. · Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Box 8100, N-4068 Stavanger, Norway. · Department of Neurology and The State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078 China. · Human Motor Control Section, NINDS, NIH, Bethesda, MD 20892-1428 Stavanger, USA. ·Sci Rep · Pubmed #27646647.

ABSTRACT: This study aimed to identify a PD-specific MRI pattern using combined diffusion tensor imaging (DTI) and arterial spin labeling (ASL) to discriminate patients with early PD from healthy subjects and evaluate disease status. Twenty-one early and 22 mid-late PD patients, and 22 healthy, age/gender-matched controls underwent 3-T MRI with apparent diffusion coefficient (ADC), fractional anisotropy (FA), fiber number (FN) and cerebral blood flow (CBF) measurements. We found that compared with healthy subjects, there was a profound reduction in FN passing through the SN in PD. FA in the SN and CBF in the caudate nucleus were inversely correlated with motor dysfunction. A negative correlation was observed between FA in the hippocampus (Hip) and the NMSS-Mood score, whereas CBF in the Hip and the prefrontal cortex(PFC) correlated with declined cognition. Stratified five-fold cross-validation identified FA in the SN(FA-SNAv), CBF in the PFC(CBF-PFCAv) and FA in the parietal white matter(FA-PWMAv), and the combination of these measurements offered relatively high accuracy (AUC 0.975, 90% sensitivity and 100% specificity) in distinguishing those with early PD from healthy subjects. We demonstrate that the decreased FNs through SN in combination with changes in FA-SNAv, CBF-PFCAv and FA-PWMAv values might serve as potential markers of early-stage PD.

4 Clinical Trial Motor symptoms after deep brain stimulation of the subthalamic nucleus. 2015

Lilleeng, B / Gjerstad, M / Baardsen, R / Dalen, I / Larsen, J P. ·The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. ·Acta Neurol Scand · Pubmed #25346142.

ABSTRACT: OBJECTIVES: Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term beneficial effects on motor symptoms in patients with Parkinson's disease (PD). The efficacy of STN-DBS on non-dopaminergic motor symptoms remains less elucidated. In this study, we have examined short- and long-term impacts of STN-DBS on the development of the postural instability and gait difficulties (PIGD) phenotype, freezing of gait (FOG), and falls. MATERIALS AND METHODS: We collected data from a prospectively followed cohort of patients that had been operated with STN-DBS 6-9 years before final examination and compared our findings to the longitudinal development of the same symptoms in a non-operated, historical reference population. RESULTS: During short-term follow-up after surgery, we observed a marked improvement in mean UPDRS-motor score from 27 to 18. We also found clear improvements in tremor, bradykinesia, rigidity, and PIGD scores. However, 6-9 years after surgery, all patients had a dominating PIGD pattern of parkinsonism and 50% of the patients had developed FOG and/or had become recurrent fallers. The disease development in a group of patients with PD from the presurgery period had a similar trajectory as among the operated patients. In addition, mean annual change of both bradykinesia and PIGD scores was nearly identical in both study groups while tremor and rigidity had a significant better development in the operated patients. CONCLUSIONS: We found that STN-DBS induces an acute improvement of PIGD symptoms. The following long-term development was however characterized by a marked progression of non-dopaminergic symptoms.

5 Article Combinatory microRNA serum signatures as classifiers of Parkinson's disease. 2019

Patil, Ketan S / Basak, Indranil / Dalen, Ingvild / Hoedt, Esthelle / Lange, Johannes / Lunde, Kristin A / Liu, Ying / Tysnes, Ole-Bjørn / Forsgren, Lars / Aarsland, Dag / Neubert, Thomas A / Larsen, Jan Petter / Alves, Guido / Møller, Simon Geir. ·Department of Biological Sciences, St. John's University, New York, NY, USA
. · Norwegian Center for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA. · Norwegian Center for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Norway. · Department of Computer Science, Mathematics and Science, St. John's University, New York, NY, USA. · Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Department of Pharmacology and Clinical Neuroscience, University of Umeå, Umeå, Sweden. · Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, UK; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. · Network for Medical Sciences, University of Stavanger, Stavanger, Norway. · Department of Biological Sciences, St. John's University, New York, NY, USA
. Electronic address: mollers@stjohns.edu. ·Parkinsonism Relat Disord · Pubmed #31003905.

ABSTRACT: INTRODUCTION: As current clinical diagnostic protocols for Parkinson's disease (PD) may be prone to inaccuracies there is a need to identify and validate molecular biomarkers, such as circulating microRNAs, which will complement current practices and increase diagnostic accuracy. This study identifies, verifies and validates combinatory serum microRNA signatures as diagnostic classifiers of PD across different patient cohorts. METHODS: 370 PD (drug naïve) and control serum samples from the Norwegian ParkWest study were used for identification and verification of differential microRNA levels in PD which were validated in a blind study using 64 NY Parkinsonism in UMeå (NYPUM) study serum samples and tested for specificity in 48 Dementia Study of Western Norway (DemWest) study Alzheimer's disease (AD) serum samples using miRNA-microarrays, and quantitative (q) RT-PCR. Proteomic approaches identified potential molecular targets for these microRNAs. RESULTS: Using Affymetrix GeneChip CONCLUSIONS: Our study has identified and validated unique miRNA serum signatures that represent PD classifiers, which may complement and increase the accuracy of current diagnostic protocols.

6 Article Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease. 2018

Lunde, Kristin Aaser / Chung, Janete / Dalen, Ingvild / Pedersen, Kenn Freddy / Linder, Jan / Domellöf, Magdalena E / Elgh, Eva / Macleod, Angus D / Tzoulis, Charalampos / Larsen, Jan Petter / Tysnes, Ole-Bjørn / Forsgren, Lars / Counsell, Carl E / Alves, Guido / Maple-Grødem, Jodi. ·The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Centre for Organelle Research, University of Stavanger, Stavanger, Norway. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Department of Neurology, Stavanger University Hospital, Stavanger, Norway. · Department of Pharmacology and Clinical Neuroscience, Neurology, Umeå University, Umeå, Sweden. · Department of Pharmacology and Clinical Neuroscience, Neurology, Umeå University, Umeå, Sweden; Department of Psychology, Umeå University, Umeå, Sweden. · Department of Psychology, Umeå University, Umeå, Sweden. · Institute of Applied Health Sciences, Polwarth Building, University of Aberdeen, Aberdeen, UK. · Department of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway. · Network for Medical Sciences, University of Stavanger, Bergen, Norway. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Department of Neurology, Stavanger University Hospital, Stavanger, Norway; Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Centre for Organelle Research, University of Stavanger, Stavanger, Norway. Electronic address: jodi.maple@uis.no. ·Alzheimers Dement · Pubmed #29792872.

ABSTRACT: INTRODUCTION: Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease. METHODS: Four hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis. RESULTS: A total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers. DISCUSSION: GBA variants are of great clinical relevance for the development of dementia in Parkinson's disease, especially due to the relatively higher frequency of these alleles compared with other risk alleles.

7 Article Development and validation of prognostic survival models in newly diagnosed Parkinson's disease. 2018

Macleod, Angus D / Dalen, Ingvild / Tysnes, Ole-Bjørn / Larsen, Jan Petter / Counsell, Carl E. ·Division of Applied Health Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK. · Department of Research, Section of Biostatistics, Stavanger University Hospital, Stavanger, Norway. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Institute of Clinical Medicine, University of Bergen, Bergen, Norway. · Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Network for Medical Sciences, University of Stavanger, Stavanger, Norway. ·Mov Disord · Pubmed #28976022.

ABSTRACT: OBJECTIVE: The objective of this study was to develop valid prognostic models to predict mortality, dependency, and "death or dependency" for use in newly diagnosed Parkinson's disease (PD). METHODS: The models were developed in the Parkinsonism Incidence in North-East Scotland study (UK, 198 patients) and validated in the ParkWest study (Norway, 192 patients), cohorts that attempted to identify and follow-up all new PD cases in the study area. Dependency was defined using the Schwab & England scale. We selected variables measured at time of diagnosis to include in the models. Internal validation and external validation were performed by calculating C-statistics (discrimination) and plotting observed versus predicted risk in quantiles of predicted risk (calibration). RESULTS: Older age, male sex, increased severity of axial features, and Charlson comorbidity index were independent prognostic factors in the mortality model. Increasing age, higher smoking history, increased severity of axial features, and lower MMSE score were independent predictors in the models of dependency and "death or dependency." Each model had very good internal calibration and very good or good discrimination (internal and external C-statistics for the models were 0.73-0.75 and 0.68-0.78, respectively). Although each model clearly separated patients into groups according to risk, they tended to overestimate risk in ParkWest. The models were recalibrated to the baseline risk in the ParkWest study and then calibrated well in this cohort. CONCLUSIONS: We have developed prognostic models for predicting medium-term risk of important clinical outcomes in newly diagnosed PD. These models have validity for use for stratification of randomization, confounder adjustment, and case-mix correction, but they are inadequate for individualized prognostication. © 2017. The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

8 Article The natural history of depressive symptoms in patients with incident Parkinson's disease: a prospective cohort study. 2017

Larsen, Jan Petter / Dalen, Ingvild / Pedersen, Kenn Freddy / Tysnes, Ole-Bjørn. ·Network for Medical Sciences, University of Stavanger, Stavanger, Norway. · Department of Research, Section of Biostatistics, Stavanger University Hospital, PO Box 8100, 4068, Stavanger, Norway. ingvild.dalen@sus.no. · Department of Neurology, Stavanger University Hospital, Stavanger, Norway. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Department of Clinical Medicine, University of Bergen, Bergen, Norway. · Department of Neurology, Haukeland University Hospital, Bergen, Norway. ·J Neurol · Pubmed #29032408.

ABSTRACT: Depression is common in patients with Parkinson disease and causes suffering and increased caregiver burden. A better understanding of depressive symptoms in Parkinson disease, their progression, and risk factors may, therefore, benefit management of these patients. The present study included 187 drug-naïve patients with incident PD and 166 controls from the population-based Norwegian ParkWest project. Depressive symptoms were examined with the Montgomery and Aasberg Depression Rating Scale (MADRS) at time of diagnosis and inclusion in the study and after 1, 3, 5, and 7 years of follow-up. Associations between MADRS scores and risk factors were assessed using generalized estimating equations (GEE). The mean MADRS score from all 823 examinations during the study period was 4.2 in patients and 1.3 in 732 examinations among controls. Among controls, the occurrence of depressive symptoms was also lower and rather stable during follow-up, while in patients, we observed a decrease from time of diagnosis and until the 1-year visit, followed by a steady increase in these symptoms over time. Factors associated with higher MADRS score in the multivariable model were female sex, being dependent, higher pain score, higher Unified PD Rating Scale (UPDRS) motor score, and lower Mini-Mental State Examination (MMSE) score. The results from this study underscore the importance and frequency of depressive symptoms in patients with early PD. Furthermore, risk factors that may be considered PD-nonspecific are associated with depressive symptoms as are factors that reflect the progression of PD.

9 Article DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis. 2017

Piston, Dominik / Alvarez-Erviti, Lydia / Bansal, Vikas / Gargano, Daniela / Yao, Zhi / Szabadkai, Gyorgy / Odell, Mark / Puno, M Rhyan / Björkblom, Benny / Maple-Grødem, Jodi / Breuer, Peter / Kaut, Oliver / Larsen, Jan Petter / Bonn, Stefan / Møller, Simon Geir / Wüllner, Ullrich / Schapira, Anthony H V / Gegg, Matthew E. ·Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK. · Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany. · Molecular Neurobiology, Centre for Biomedical Research of Rioja, Logrono, Spain. · Centre for Organelle Research, University of Stavanger, Stavanger, Norway. · Department of Cell and Developmental Biology, Consortium for Mitochondrial Research, University College London, London, UK. · Department of Molecular and Applied Biosciences, University of Westminster, London, UK. · Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden. · Department of Neurology, University of Bonn Medical Centre, Bonn, Germany. · Department of Biological Sciences, St. John's University, New York, NY, USA. ·Hum Mol Genet · Pubmed #29016861.

ABSTRACT: DJ-1 is an oxidation sensitive protein encoded by the PARK7 gene. Mutations in PARK7 are a rare cause of familial recessive Parkinson's disease (PD), but growing evidence suggests involvement of DJ-1 in idiopathic PD. The key clinical features of PD, rigidity and bradykinesia, result from neurotransmitter imbalance, particularly the catecholamines dopamine (DA) and noradrenaline. We report in human brain and human SH-SY5Y neuroblastoma cell lines that DJ-1 predominantly forms high molecular weight (HMW) complexes that included RNA metabolism proteins hnRNPA1 and PABP1 and the glycolysis enzyme GAPDH. In cell culture models the oxidation status of DJ-1 determined the specific complex composition. RNA sequencing indicated that oxidative changes to DJ-1 were concomitant with changes in mRNA transcripts mainly involved in catecholamine metabolism. Importantly, loss of DJ-1 function upon knock down (KD) or expression of the PD associated form L166P resulted in the absence of HMW DJ-1 complexes. In the KD model, the absence of DJ-1 complexes was accompanied by impairment in catecholamine homeostasis, with significant increases in intracellular DA and noraderenaline levels. These changes in catecholamines could be rescued by re-expression of DJ-1. This catecholamine imbalance may contribute to the particular vulnerability of dopaminergic and noradrenergic neurons to neurodegeneration in PARK7-related PD. Notably, oxidised DJ-1 was significantly decreased in idiopathic PD brain, suggesting altered complex function may also play a role in the more common sporadic form of the disease.

10 Article The GBA variant E326K is associated with Parkinson's disease and explains a genome-wide association signal. 2017

Berge-Seidl, Victoria / Pihlstrøm, Lasse / Maple-Grødem, Jodi / Forsgren, Lars / Linder, Jan / Larsen, Jan Petter / Tysnes, Ole-Bjørn / Toft, Mathias. ·Department of Neurology, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: berge.victoria@gmail.com. · Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: lasse.pihlstrom@gmail.com. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; The Centre for Organelle Research, University of Stavanger, Stavanger, Norway. Electronic address: jodi.maple.grodem@sus.no. · Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden. Electronic address: lars.forsgren@umu.se. · Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden. Electronic address: jan.linder@umu.se. · Network for Medical Sciences, University of Stavanger, Stavanger, Norway. Electronic address: nevrologlarsen@gmail.com. · Department of Neurology, Haukeland University Hospital, Bergen, Norway. Electronic address: ole-bjorn.tysnes@helse-bergen.no. · Department of Neurology, Oslo University Hospital, Oslo, Norway. Electronic address: mathias.toft@gmail.com. ·Neurosci Lett · Pubmed #28830825.

ABSTRACT: OBJECTIVE: Coding variants in the GBA gene have been identified as the numerically most important genetic risk factors for Parkinson's disease (PD). In addition, genome-wide association studies (GWAS) have identified associations with PD in the SYT11-GBA region on chromosome 1q22, but the relationship to GBA coding variants have remained unclear. The aim of this study was to sequence the complete GBA gene in a clinical cohort and to investigate whether coding variants within the GBA gene may be driving reported association signals. METHODS: We analyzed high-throughput sequencing data of all coding exons of GBA in 366 patients with PD. The identified low-frequency coding variants were genotyped in three Scandinavian case-controls series (786 patients and 713 controls). Previously reported risk variants from two independent association signals within the SYT11-GBA locus on chromosome 1 were also genotyped in the same samples. We performed association analyses and evaluated linkage disequilibrium (LD) between the variants. RESULTS: We identified six rare mutations (1.6%) and two low-frequency coding variants in GBA. E326K (rs2230288) was significantly more frequent in PD patients compared to controls (OR 1.65, p=0.03). There was no clear association of T369M (rs75548401) with disease (OR 1.43, p=0.24). Genotyping the two GWAS hits rs35749011 and rs114138760 in the same sample set, we replicated the association between rs35749011 and disease status (OR 1.67, p=0.03), while rs114138760 was found to have similar allele frequencies in patients and controls. Analyses revealed that E326K and rs35749011 are in very high LD (r CONCLUSIONS: Our results confirm that the GBA variant E326K is a susceptibility allele for PD. The results suggest that E326K may fully account for the primary association signal observed at chromosome 1q22 in previous GWAS of PD.

11 Article Natural course of mild cognitive impairment in Parkinson disease: A 5-year population-based study. 2017

Pedersen, Kenn Freddy / Larsen, Jan Petter / Tysnes, Ole-Bjørn / Alves, Guido. ·From the Norwegian Centre for Movement Disorders (K.F.P., G.A.) · Department of Neurology (K.F.P., G.A.) and Memory Clinic (K.F.P., G.A.), Stavanger University Hospital · Network for Medical Sciences (J.P.L.), University of Stavanger · and Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway. ·Neurology · Pubmed #28108638.

ABSTRACT: OBJECTIVE: To examine the incidence, progression, and reversion of mild cognitive impairment in patients with Parkinson disease (PD-MCI) over 5 years. METHODS: A population-based cohort of patients with incident PD underwent repeated neuropsychological testing of attention, executive function, memory, and visuospatial abilities at baseline (n = 178), 1 year (n = 175), 3 years (n = 163), and 5 years (n = 150). Patients were classified as PD-MCI and diagnosed with dementia according to published criteria. RESULTS: Thirty-six patients (20.2%) fulfilled criteria for PD-MCI at baseline. Among those with normal cognition at baseline (n = 142), the cumulative incidence of PD-MCI was 9.9% after 1 year, 23.2% after 3 years, and 28.9% after 5 years of follow-up. Overall, 39.1% of patients with baseline or incident PD-MCI progressed to dementia during the 5-year study period. The conversion rate to dementia was 59.1% in patients with persistent PD-MCI at 1 year vs 7.2% in those with normal cognition during the first year (adjusted odds ratio 16.6, 95% confidence interval 5.1-54.7, CONCLUSIONS: Early PD-MCI, regardless of persistence or reversion to normal cognition, has prognostic value for predicting dementia in patients with PD.

12 Article Long-term risk of falls in an incident Parkinson's disease cohort: the Norwegian ParkWest study. 2017

Hiorth, Ylva Hivand / Alves, Guido / Larsen, Jan Petter / Schulz, Jörn / Tysnes, Ole-Bjørn / Pedersen, Kenn Freddy. ·The Norwegian Centre for Movement Disorders, Stavanger University Hospital, PO Box 8100, 4068, Stavanger, Norway. ylvahi@sus.no. · Department of Physical Medicine and Rehabilitation, Stavanger University Hospital, Stavanger, Norway. ylvahi@sus.no. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, PO Box 8100, 4068, Stavanger, Norway. · Department of Neurology, Stavanger University Hospital, Stavanger, Norway. · Network for Medical Sciences, University of Stavanger, Stavanger, Norway. · Department of Electrical Engineering and Computer Science, University of Stavanger, Stavanger, Norway. · Department of Clinical Medicine, University of Bergen, Bergen, Norway. · Department of Neurology, Haukeland University Hospital, Bergen, Norway. ·J Neurol · Pubmed #28000003.

ABSTRACT: The objective of this study is to examine the frequency, development, concomitants, and risk factors of falls in a population-based incident Parkinson's disease (PD) cohort. One hundred eighty-one drug-naïve patients with incident PD and 173 normal controls recruited from the Norwegian ParkWest study were prospectively monitored over 7 years. Information on falls was obtained biannually from patients, and at baseline and after 1, 3, 5, and 7 years of follow-up in control subjects. Generalized estimating equation models for correlated data were applied to investigate concomitant features of falls and risk factors for incident falls during 7 years of follow-up in PD. Overall, 64.1% of patients reported falling during the study period. The 7-year cumulative incidence of falls in non-falling patients at baseline (n = 153) was 57.5%, with a relative risk to controls of at least 3.1 (95% confidence interval 1.5-6.3; p < 0.002). Significant concomitants of falls in patients during the study period were higher age, Unified PD Rating Scale motor score, postural instability and gait difficulties (PIGD) phenotype, dementia, and follow-up time. Higher age at baseline, PIGD phenotype at 1-year visit, and follow-up time were independent risk factors for incident falls during follow-up. Nearly two-thirds of patients in the general PD population experience falls within 7 years of diagnosis, representing a more than threefold increased risk compared to age- and gender-matched controls. Patients with higher age at baseline and early PIGD have the greatest risk of falling and may, therefore, be the prime target of specialized assessment and treatment interventions.

13 Article Changes in insomnia subtypes in early Parkinson disease. 2017

Tholfsen, Lena K / Larsen, Jan P / Schulz, Jörn / Tysnes, Ole-Bjørn / Gjerstad, Michaela D. ·From the Norwegian Centre for Movement Disorders (L.K.T., J.S., M.D.G.) and Department of Neurology (L.K.T., M.D.G.), Stavanger University Hospital · Network for Medical Sciences (J.P.L.), Faculty of Social Sciences, University of Stavanger · and Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway. ·Neurology · Pubmed #27986876.

ABSTRACT: OBJECTIVE: To examine the development of factors associated with insomnia in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. METHODS: One hundred eighty-two drug-naive patients with PD derived from a population-based incident cohort and 202 control participants were assessed for insomnia before treatment initiation and were repeatedly examined after 1, 3, and 5 years. Insomnia was diagnosed according to the Stavanger Sleepiness Questionnaire. The Parkinson's Disease Sleep Scale was used to differentiate sleep initiation problems from problems of sleep maintenance. Generalized estimating equation models were applied for statistical measures. RESULTS: The prevalence of insomnia in general was not higher in patients with PD compared to controls at the 5-year follow-up. There were changes in the prevalence of the different insomnia subtypes over the 5-year follow-up. The prevalence of solitary problems in sleep maintenance increased from 31% (n = 18) in the drug-naive patients at baseline to 49% (n = 29) after 1 year and were associated with the use of dopamine agonists and higher Montgomery-Åsberg Depression Rating Scale scores. The prevalence of solitary sleep initiation problems decreased continuously from 21% (n = 12) at baseline to 7.4% (n = 4) after 5 years; these were associated with less daytime sleepiness. CONCLUSIONS: The prevalence rates of the different insomnia subtypes changed notably in patients with early PD. The frequency of sleep maintenance problems increased, and these problems were associated with dopamine agonist use and depressive symptoms, while the total number of patients with insomnia remained stable. Our findings reflect the need for early individual assessments of insomnia subtypes and raise the possibility of intervention to reduce these symptoms in patients with early PD.

14 Article Impulsive and Compulsive Behaviors in Parkinson's Disease: The Norwegian ParkWest Study. 2017

Erga, Aleksander H / Alves, Guido / Larsen, Jan Petter / Tysnes, Ole Bj Rn / Pedersen, Kenn Freddy. ·The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Department of Neurology, Stavanger University Hospital, Stavanger, Norway. · Network for Medical Sciences, University of Stavanger, Stavanger, Norway. · Department of Neurology, Haukeland University Hospital, Bergen, Norway. ·J Parkinsons Dis · Pubmed #27911342.

ABSTRACT: BACKGROUND: Impulsive and compulsive behaviors (ICBs) are frequent in Parkinson's disease (PD), but data from population-based cohorts is lacking. OBJECTIVES: To determine the frequency and associated demographic, clinical, neuropsychiatric and cognitive features of ICBs in a population-based PD cohort. METHODS: This cross-sectional study included 125 patients with PD and 159 age- and gender-matched normal controls recruited from the Norwegian ParkWest study. Participants underwent comprehensive neurological, neuropsychiatric and neuropsychological assessments. ICBs were assessed using the Questionnaire for Impulsive-Compulsive Disorders in PD short form. Multiple logistic regression analyses were performed to compare the odds of ICBs between groups and to identify independent correlates of ICBs in PD. RESULTS: 30.4% of patients reported at least one ICB, with an odds ratio (OR) of 3.2 (95% confidence interval [CI] 1.8-5.9) compared with controls. Multiple ICBs were experienced by 8.8% of patients vs 1.3% of controls (OR 7.6, 95% CI 1.7-34.8). Compared to controls, the ORs of having an ICB were 7.4 (95% CI 2.6-20.9) in patients taking DA without levodopa, 4.6 (95% CI 2.3-9.3) in those treated with both DA and levodopa, and 1.2 (95% CI 0.5-3.2) in patients using levodopa but not DA. In multivariate models, ICB status in patients was independently associated with DA treatment and depressive symptoms, but not with other dopaminergic medications, motor function, or cognitive performance. CONCLUSIONS: Patients with PD treated with DA, but not other dopaminergic medications, have increased odds of having ICBs compared with age- and gender-matched controls. This has implications for individualized patient management and follow-up.

15 Article Familial aggregation of Parkinson's disease may affect progression of motor symptoms and dementia. 2017

Gaare, Johannes Jernqvist / Skeie, Geir Olve / Tzoulis, Charalampos / Larsen, Jan Petter / Tysnes, Ole-Bjørn. ·Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Department of Clinical Medicine, University of Bergen, Bergen, Norway. · Network for Medical Sciences, University of Stavanger, Stavanger, Norway. ·Mov Disord · Pubmed #27862270.

ABSTRACT: BACKGROUND: Familial aggregation has been described in PD of both early and late onset, but has not been studied in a true population-based sample. Moreover, little is known about its association with disease progression and endophenotypes. OBJECTIVES: The objectives of this work were to determine familial aggregation of idiopathic PD in a population-based cohort and study the association with clinical endophenotypes and disease progression. METHODS: We examined family history data from the Norwegian ParkWest study, a well-characterized, population-based cohort of incident PD patients and age-matched healthy controls. Family data were collected at baseline with a simplified questionnaire (192 cases and 193 controls) and after 3 years of longitudinal follow-up using an extended questionnaire (172 cases and 171 controls). RESULTS: Compared to the controls, the PD patients had an increased relative risk of having a first-degree relative with PD when using the extended questionnaire (relative risk = 1.988; P = 0.036), but not when using the simplified questionnaire (relative risk = 1.453; P = 0.224). There was no significant difference in age of onset or motor subtype (P = 0.801). However, cases with a family history of PD had reduced progression over 7 years as measured by UPDRS II (P = 0.008) and smaller rate of decrease of MMSE (P = 0.046). CONCLUSIONS: Our findings confirm familial aggregation in a population-based cohort of idiopathic PD. Moreover, we show that positive family history of PD in patients is associated with a slower progression of PD symptoms and cognitive decline. © 2016 International Parkinson and Movement Disorder Society.

16 Article Subcellular Parkinson's Disease-Specific Alpha-Synuclein Species Show Altered Behavior in Neurodegeneration. 2017

Abdullah, Rashed / Patil, Ketan S / Rosen, Benjamin / Pal, Ramavati / Prabhudesai, Shubhangi / Lee, Sungsu / Basak, Indranil / Hoedt, Esthelle / Yang, Peter / Panick, Keith / Ho, Hsin-Pin / Chang, Emmanuel / Tzoulis, Charalampos / Larsen, Jan Petter / Neubert, Thomas A / Alves, Guido / Møller, Simon G. ·Department of Biological Sciences, St. John's University, New York, NY, 11349, USA. · Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, 10016, USA. · Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA. · Department of Chemistry, York College of the City University of New York, New York, NY, 11451, USA. · Center for Mitochondrial Medicine and Neurogenetics, Department of Neurology, Haukeland University Hospital, 5021, Bergen, Norway. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, 4068, Stavanger, Norway. · Department of Biological Sciences, St. John's University, New York, NY, 11349, USA. mollers@stjohns.edu. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, 4068, Stavanger, Norway. mollers@stjohns.edu. ·Mol Neurobiol · Pubmed #27837450.

ABSTRACT: Parkinson's disease and other synucleinopathies are characterized by the presence of intra-neuronal protein aggregates enriched in the presynaptic protein α-synuclein. α-synuclein is considered an intrinsically disordered 14 kDa monomer, and although poorly understood, its transition to higher-order multimeric species may play central roles in healthy neurons and during Parkinson's disease pathogenesis. In this study, we demonstrate that α-synuclein exists as defined, subcellular-specific species that change characteristics in response to oxidative stress in neuroblastoma cells and in response to Parkinson's disease pathogenesis in human cerebellum and frontal cortex. We further show that the phosphorylation patterns of different α-synuclein species are subcellular specific and dependent on the oxidative environment. Using high-performance liquid chromatography and mass spectrometry, we identify a Parkinson's disease enriched, cytosolic ~36-kDa α-synuclein species which can be recapitulated in Parkinson's disease model neuroblastoma cells. The characterization of subcellular-specific α-synuclein features in neurodegeneration will allow for the identification of neurotoxic α-synuclein species, which represent prime targets to reduce α-synuclein pathogenicity.

17 Article Fatigue in early Parkinson's disease: the Norwegian ParkWest study. 2017

Ongre, S O / Larsen, J P / Tysnes, O B / Herlofson, K. ·Department of Neurology, Sorlandet Hospital, Arendal, Norway. · Network for Medical Sciences, University of Stavanger, Stavanger, Norway. · Department of Neurology, Haukeland University Hospital, Bergen, Norway. ·Eur J Neurol · Pubmed #27670392.

ABSTRACT: BACKGROUND AND PURPOSE: Fatigue is a common and disabling non-motor symptom in Parkinson's disease (PD). The pathogenesis is unknown, and the treatment options are limited. The aim of the present study was to investigate the development of fatigue during the first year after diagnosis. METHODS: The study design was a prospective, controlled population-based longitudinal cohort study, comprising 181 de novo, drug-naïve patients with PD and 162 control participants. PD was diagnosed according to the Gelb criteria. Fatigue was assessed by the Fatigue Severity Scale (FSS). Both groups were assessed for fatigue at baseline and after 1 year. RESULTS: Patients reported more fatigue than the control subjects at baseline and at the 1-year follow-up evaluation. The FSS scores in the patient group improved from a mean score of 4.4 (SD 1.6) to 4.0 (SD 1.6). Patients with fatigue at baseline received higher doses of dopaminergic medication during follow-up. Patients who received dopamine agonists improved slightly more than patients who received levodopa. A regression analysis did not show a correlation between an improvement in fatigue and a change in disease severity, depressive symptoms, sleep problems, apathy or cognitive impairment. CONCLUSION: Fatigue is a common symptom in PD, also in early, untreated patients. During the first year of observation, an improvement in the fatigue scores was found. The improvement could not be attributed to a change in disease severity or depressive symptoms. The results indicate a better effect of dopamine agonists than of levodopa. This may have implications for treatment in patients with PD-associated fatigue.

18 Article Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease. 2016

Dölle, Christian / Flønes, Irene / Nido, Gonzalo S / Miletic, Hrvoje / Osuagwu, Nelson / Kristoffersen, Stine / Lilleng, Peer K / Larsen, Jan Petter / Tysnes, Ole-Bjørn / Haugarvoll, Kristoffer / Bindoff, Laurence A / Tzoulis, Charalampos. ·Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway. · Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway. · Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway. · Department of Biomedicine, University of Bergen, 5020 Bergen, Norway. · Gade Laboratory for Pathology, Department of Clinical Medicine, Haukeland University Hospital and University of Bergen, 5021 Bergen, Norway. · Network for Medical Sciences, University of Stavanger, 4036 Stavanger, Norway. ·Nat Commun · Pubmed #27874000.

ABSTRACT: Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we study the complete spectrum of mtDNA changes, including deletions, copy-number variation and point mutations, in single neurons from the dopaminergic substantia nigra and other brain areas of individuals with Parkinson disease and neurologically healthy controls. We show that in dopaminergic substantia nigra neurons of healthy individuals, mtDNA copy number increases with age, maintaining the pool of wild-type mtDNA population in spite of accumulating deletions. This upregulation fails to occur in individuals with Parkinson disease, however, resulting in depletion of the wild-type mtDNA population. By contrast, neuronal mtDNA point mutational load is not increased in Parkinson disease. Our findings suggest that dysregulation of mtDNA homeostasis is a key process in the pathogenesis of neuronal loss in Parkinson disease.

19 Article Loss of independence in early Parkinson disease: A 5-year population-based incident cohort study. 2016

Bjornestad, Anders / Tysnes, Ole-Bjorn / Larsen, Jan Petter / Alves, Guido. ·From The Norwegian Centre for Movement Disorders (A.B., J.P.L., G.A.) and Department of Neurology (A.B., G.A.), Stavanger University Hospital · Department of Neurology (O.-B.T.), Haukeland University Hospital · and Institute of Clinical Medicine (O.-B.T.), University of Bergen, Norway. ·Neurology · Pubmed #27590290.

ABSTRACT: OBJECTIVE: To determine the risk, predictors, and prognosis of independence loss and institutionalization in patients with early Parkinson disease (PD). METHODS: We conducted a prospective population-based 5-year longitudinal study following 189 patients with incident PD and 174 controls matched for age, sex, and comorbidity. Health care status was assessed repeatedly with standardized interviews. RESULTS: More newly diagnosed patients with PD (15.9%) than controls (5.7%) were dependent in activities of daily living at baseline (relative risk [RR] 2.8, p = 0.004). During follow-up, 40.9% of the initially independent patients lost their independence vs 9.1% of controls (RR 4.5, p < 0.001). Higher age, shorter symptom duration, increasing motor severity, and presence of mild cognitive impairment at PD diagnosis independently predicted independence loss during follow-up. Dependency was irreversible in most (>95%) patients. Long-term care facility placement was needed in 8.8% of patients vs 0.6% of controls (RR 15.4, p = 0.001). More patients with PD admitted to long-term care facilities were fallers (RR 4.8, p < 0.001), had hallucinations (RR 4.4, p = 0.001), or had dementia (RR 4.2, p < 0.001) than home-dwelling patients. Once admitted to a long-term care facility, the age-adjusted RR for death during the study period was 5.5 (p = 0.002) vs patients never admitted and 25.1 (p < 0.001) vs controls. CONCLUSIONS: Patients with early PD face a substantially greater risk of independence loss and institutionalization than well-matched controls. Independence loss is irreversible in most patients and represents a sinister prognostic factor in early PD. These findings have implications for patient management and health care planning.

20 Article LRRK2 knockdown in zebrafish causes developmental defects, neuronal loss, and synuclein aggregation. 2016

Prabhudesai, Shubhangi / Bensabeur, Fatima Zahra / Abdullah, Rashed / Basak, Indranil / Baez, Solange / Alves, Guido / Holtzman, Nathalia G / Larsen, Jan Petter / Møller, Simon Geir. ·Department of Biological Sciences, St. John's University, Queens, New York. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Department of Biology, Queens College and The Graduate Center, CUNY, Queens, New York. ·J Neurosci Res · Pubmed #27265751.

ABSTRACT: Although mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinson's disease, their function is largely unknown. LRRK2 is pleiotropic in nature, shown to be involved in neurodegeneration and in more peripheral processes, including kidney functions, in rats and mice. Recent studies in zebrafish have shown conflicting evidence that removal of the LRRK2 WD40 domain may or may not affect dopaminergic neurons and/or locomotion. This study shows that ∼50% LRRK2 knockdown in zebrafish causes not only neuronal loss but also developmental perturbations such as axis curvature defects, ocular abnormalities, and edema in the eyes, lens, and otic vesicles. We further show that LRRK2 knockdown results in significant neuronal loss, including a reduction of dopaminergic neurons. Immunofluorescence demonstrates that endogenous LRRK2 is expressed in the lens, brain, heart, spinal cord, and kidney (pronephros), which mirror the LRRK2 morphant phenotypes observed. LRRK2 knockdown results further in the concomitant upregulation of β-synuclein, PARK13, and SOD1 and causes β-synuclein aggregation in the diencephalon, midbrain, hindbrain, and postoptic commissure. LRRK2 knockdown causes mislocalization of the Na(+) /K(+) ATPase protein in the pronephric ducts, suggesting that the edema might be linked to renal malfunction and that LRRK2 might be associated with pronephric duct epithelial cell differentiation. Combined, our study shows that LRRK2 has multifaceted roles in zebrafish and that zebrafish represent a complementary model to further our understanding of this central protein. © 2016 Wiley Periodicals, Inc.

21 Article Impact of Falls on Physical Activity in People with Parkinson's Disease. 2016

Hiorth, Ylva Hivand / Larsen, Jan Petter / Lode, Kirsten / Tysnes, Ole-Bjørn / Godfrey, Alan / Lord, Sue / Rochester, Lynn / Pedersen, Kenn Freddy. ·The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · Department of Physical Medicine and Rehabilitation, Stavanger University Hospital, Stavanger, Norway. · Department of Research, Stavanger University Hospital, Stavanger, Norway. · Department of Clinical Medicine, University of Bergen, Bergen, Norway. · Department of Neurology, Haukeland University Hospital, Bergen, Norway. · Institute of Neuroscience, Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK. · Department of Neurology, Stavanger University Hospital, Stavanger, Norway. ·J Parkinsons Dis · Pubmed #26639446.

ABSTRACT: BACKGROUND: A complex relationship exists between motor impairment, physical activity (sedentary behavior, standing and ambulatory activity) and falls in people with Parkinson's disease (PD). OBJECTIVE: To explore associations between recent fall history and the ability to retain an active lifestyle as determined by the volume, pattern and variability of physical activity in people with PD. METHODS: Forty-eight participants with PD were recruited from the Norwegian ParkWest study. Body posture and ambulatory activity were monitored objectively over 7 days using the activPAL3 accelerometer. Clinical assessments included the Hoehn and Yahr stage, Unified Parkinson's Disease Rating Scale motor section and Falls Efficacy Scale-International. Structured interviews were performed to obtain information about demographics, fall history last 6 months, mobility and dementia. RESULTS: Participants with a fall history (n = 20) spent more time sedentary and less time standing than non-falling participants (n = 28). There were no significant differences regarding pattern or variability of sedentary behavior, standing or ambulatory activity in falling versus non-falling participants. Confidence in being able to get up from floor contributed significantly to time spent in sedentary behavior and ambulatory activity in participants with fall history, whereas motor impairment was significantly associated with time spent in all facets of physical activity for non-falling participants. CONCLUSIONS: Fall history in our PD cohort was associated with a more sedentary lifestyle, but not less ambulatory activity. More emphasis on improving the capacity to safely complete activities of daily living and increase confidence in getting up from floor may reduce sedentary behavior in people with PD.

22 Article Risk and course of motor complications in a population-based incident Parkinson's disease cohort. 2016

Bjornestad, Anders / Forsaa, Elin B / Pedersen, Kenn Freddy / Tysnes, Ole-Bjorn / Larsen, Jan Petter / Alves, Guido. ·The Norwegian Centre for Movement Disorders, Stavanger University Hospital, PO Box 8100, N-4068 Stavanger, Norway; Department of Neurology, Stavanger University Hospital, Stavanger, Norway. Electronic address: anders.bjornestad@outlook.com. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, PO Box 8100, N-4068 Stavanger, Norway; Department of Neurology, Stavanger University Hospital, Stavanger, Norway. Electronic address: elin.bjelland.forsaa@sus.no. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, PO Box 8100, N-4068 Stavanger, Norway; Department of Neurology, Stavanger University Hospital, Stavanger, Norway. Electronic address: kenn.freddy.pedersen@sus.no. · Department of Neurology, Haukeland University Hospital, PO Box 1400, N-5021 Bergen, Norway; Institute of Clinical Medicine, University of Bergen, Norway. Electronic address: ole-bjorn.tysnes@helse-bergen.no. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, PO Box 8100, N-4068 Stavanger, Norway. Electronic address: jpl@sus.no. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, PO Box 8100, N-4068 Stavanger, Norway; Department of Neurology, Stavanger University Hospital, Stavanger, Norway. Electronic address: algu@sus.no. ·Parkinsonism Relat Disord · Pubmed #26585090.

ABSTRACT: BACKGROUND: Motor complications may become major challenges in the management of patients with Parkinson's disease. In this study, we sought to determine the incidence, risk factors, evolution, and treatment of motor fluctuations and dyskinesias in a population-representative, incident Parkinson's disease cohort. METHODS: In this prospective population-based 5-year longitudinal study, we followed 189 incident and initially drug-naïve Parkinson's disease patients biannually for detailed examination of dyskinesias and motor fluctuations as defined by the Unified Parkinson's disease Rating Scale. We performed Kaplan-Meier survival and Cox regression analyses to assess cumulative incidence and risk factors of these motor complications. RESULTS: The 5-year cumulative incidence of motor complications was 52.4%. Motor fluctuations occurred in 42.9% and dyskinesias in 24.3%. Besides higher motor severity predicting both motor fluctuations (p = 0.016) and dyskinesias (p < 0.001), lower age at diagnosis predicted motor fluctuations (p = 0.001), whereas female gender predicted dyskinesias (p = 0.001). Actual levodopa dose at onset of motor fluctuations (p = 0.037) or dyskinesias (p < 0.001) rather than initial treatment with levodopa (p > 0.1) independently predicted development of motor complications. Motor fluctuations reversed in 37% and dyskinesias in 49% of patients on oral treatment and remained generally mild in those with persistent complications. No patients received device-aided therapies during the study. CONCLUSIONS: More than 50% in the general Parkinson's disease population develop motor complications within 5 years of diagnosis. However, they remain mild in the vast majority and are reversible in a substantial proportion of patients.

23 Article Edaravone leads to proteome changes indicative of neuronal cell protection in response to oxidative stress. 2015

Jami, Mohammad-Saeid / Salehi-Najafabadi, Zahra / Ahmadinejad, Fereshteh / Hoedt, Esthelle / Chaleshtori, Morteza Hashemzadeh / Ghatrehsamani, Mahdi / Neubert, Thomas A / Larsen, Jan Petter / Møller, Simon Geir. ·Department of Biological Sciences, St John's University, New York, NY, USA; Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: sjamif@gmail.com. · Department of Biological Sciences, St John's University, New York, NY, USA. Electronic address: Zahra.salehi@live.com. · Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: Fereshte.ahmadi86@ymail.com. · Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA. Electronic address: Esthelle.Hoedt@med.nyu.edu. · Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: mchalesh@yahoo.com. · Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. · Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA. Electronic address: Thomas.Neubert@med.nyu.edu. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Norway. Electronic address: jpl@sus.no. · Department of Biological Sciences, St John's University, New York, NY, USA; The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Norway. Electronic address: mollers@stjohns.edu. ·Neurochem Int · Pubmed #26232623.

ABSTRACT: Neuronal cell death, in neurodegenerative disorders, is mediated through a spectrum of biological processes. Excessive amounts of free radicals, such as reactive oxygen species (ROS), has detrimental effects on neurons leading to cell damage via peroxidation of unsaturated fatty acids in the cell membrane. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been used for neurological recovery in several countries, including Japan and China, and it has been suggested that Edaravone may have cytoprotective effects in neurodegeneration. Edaravone protects nerve cells in the brain by reducing ROS and inhibiting apoptosis. To gain further insight into the cytoprotective effects of Edaravone against oxidative stress condition we have performed comparative two-dimensional gel electrophoresis (2DE)-based proteomic analyses on SH-SY5Y neuroblastoma cells exposed to oxidative stress and in combination with Edaravone. We showed that Edaravone can reverse the cytotoxic effects of H2O2 through its specific mechanism. We observed that oxidative stress changes metabolic pathways and cytoskeletal integrity. Edaravone seems to reverse the H2O2-mediated effects at both the cellular and protein level via induction of Peroxiredoxin-2.

24 Article Development of excessive daytime sleepiness in early Parkinson disease. 2015

Tholfsen, Lena K / Larsen, Jan P / Schulz, Jörn / Tysnes, Ole-Bjorn / Gjerstad, Michaela D. ·From The Norwegian Centre for Movement Disorders (L.K.T., J.P.L., J.S., M.D.G.), Stavanger · Department of Neurology (L.K.T., M.D.G.), Stavanger University Hospital · and Department of Neurology (O-B.T.), Haukeland University Hospital, Bergen, Norway. ·Neurology · Pubmed #26085603.

ABSTRACT: OBJECTIVE: To examine the frequency, development, and risk factors of excessive daytime sleepiness (EDS) in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. METHODS: One hundred fifty-three drug-naive patients with early PD derived from a population-based incident cohort and 169 control participants were assessed for EDS and reevaluated after 1, 3, and 5 years on medication. EDS was diagnosed according to the Epworth Sleepiness Scale. Cutoff score above 10 was applied. Generalized estimating equation models for correlated data were used to examine associated and risk factors for EDS. RESULTS: Patients reported EDS more often than control participants at the time of diagnosis and during follow-up. The frequency of EDS in PD increased from 11.8% at baseline to 23.4% after 5 years. Associated factors were male sex, the use of dopamine agonists, and higher Montgomery-Åsberg Depression Rating Scale and Unified Parkinson's Disease Rating Scale-activities of daily living scores. Main risk factor for developing EDS was an increased Epworth Sleepiness Scale score at baseline. CONCLUSION: EDS is more frequent in PD even before treatment initiation compared with control participants and increases in occurrence with disease progression. The main risk factor for developing EDS with time is an early predisposition for sleepiness. In addition, the use of dopamine agonists was associated with the development of EDS. These findings necessitate caution in patients with PD and early increased sleep propensity and when using dopamine agonists.

25 Article The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease. 2015

Lill, Christina M / Rengmark, Aina / Pihlstrøm, Lasse / Fogh, Isabella / Shatunov, Aleksey / Sleiman, Patrick M / Wang, Li-San / Liu, Tian / Lassen, Christina F / Meissner, Esther / Alexopoulos, Panos / Calvo, Andrea / Chio, Adriano / Dizdar, Nil / Faltraco, Frank / Forsgren, Lars / Kirchheiner, Julia / Kurz, Alexander / Larsen, Jan P / Liebsch, Maria / Linder, Jan / Morrison, Karen E / Nissbrandt, Hans / Otto, Markus / Pahnke, Jens / Partch, Amanda / Restagno, Gabriella / Rujescu, Dan / Schnack, Cathrin / Shaw, Christopher E / Shaw, Pamela J / Tumani, Hayrettin / Tysnes, Ole-Bjørn / Valladares, Otto / Silani, Vincenzo / van den Berg, Leonard H / van Rheenen, Wouter / Veldink, Jan H / Lindenberger, Ulman / Steinhagen-Thiessen, Elisabeth / Anonymous8670828 / Teipel, Stefan / Perneczky, Robert / Hakonarson, Hakon / Hampel, Harald / von Arnim, Christine A F / Olsen, Jørgen H / Van Deerlin, Vivianna M / Al-Chalabi, Ammar / Toft, Mathias / Ritz, Beate / Bertram, Lars. ·Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. Electronic address: christina.lill@gmx.de. · Department of Neurology, Oslo University Hospital, Oslo, Norway. · Department of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, UK. · Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Human Genetics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. · Max Planck Institute for Human Development, Berlin, Germany. · Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. · Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. · Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany. · Rita Levi Montalcini Department of Neuroscience, ALS Center, University of Torino, Torino, Italy. · Rita Levi Montalcini Department of Neuroscience, ALS Center, University of Torino, Torino, Italy; Neuroscience Institute of Turin, Turin, Italy. · Department of Neurology, Linköping University, Linköping, Sweden. · Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University of Frankfurt, Frankfurt, Germany. · Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden. · Department of Neurology, University of Ulm, Ulm, Germany. · The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. · School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; Neurosciences Division, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. · Department of Pharmacology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. · Department of Neuro-/Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway; Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany. · Department of Clinical Pathology, Molecular Genetics Unit, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy. · Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany. · Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK. · Department of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway. · Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milano, Italy; Department of Pathophysiology and Tranplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milano, Italy. · Department of Neurology, Neuromuscular Diseases Brain Center Rudolf Magnus, Netherlands ALS Center, University Medical Center Utrecht, Utrecht, The Netherlands. · Interdisciplinary Metabolic Center, Lipids Clinic, Charité University Medicine, Berlin, Germany. · German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany. · Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London, UK; West London Cognitive Disorders Treatment and Research Unit, West London Mental Health Trust, London, UK. · AXA Research Fund & UPMC Chair, Paris, France; Département de Neurologie, Sorbonne Universités, Université Pierre et Marie Curie, Institut de la Mémoire et de la Maladie d'Alzheimer & Institut du Cerveau et de la Moelle épinière (ICM), Hôpital de la Pitié-Salpétrière, Paris, France. · Department of Epidemiology and Environmental Sciences, School of Public Health, University of California, Los Angeles, CA, USA. · Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London, UK. ·Alzheimers Dement · Pubmed #25936935.

ABSTRACT: A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.

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